Forsyth, PeterKurz, EbbaMcKenzie, Brienne Alexandra2012-12-202013-06-152012-12-202012McKenzie, B. A. (2012). Myxoma Virus Treatment for Brain Tumour Initiating Cells: Interrogating and Enhancing Myxoma-Mediated Cell Death (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/27050http://hdl.handle.net/11023/368Brain tumour initiating cells (BTICs) are stem-like cells hypothesized to mediate recurrence in high-grade gliomas. Preclinical success has been demonstrated in treating patient-derived BTICs with oncolytic virotherapy, using replication-competent viruses to target and kill malignant cells. Myxoma virus (MyxV) is an oncolytic candidate, which is highly effective in conventional glioma models, but only modestly effective in BTICs. The objective of this study was to improve MyxV efficacy in BTICs in vitro, combining chemotherapeutics and virotherapy. Using a pharmacoviral screen, eleven compounds that enhance MyxV-mediated cell death were identified. A lead compound, axitinib, was validated in multiple BTIC models. It was demonstrated that a virally encoded protein, M011L, prevents MyxV-induced apoptosis in BTICs, and M011L disruption was shown to greatly improve MyxV-mediated cell death through apoptosis induction. These studies have elucidated multiple strategies for improving MyxV efficacy in a preclinical glioma model, with implications for the future clinical development of MyxV.engUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.Health Sciencesglioblastomamyxoma virusbrain tumour stem cellsmaster thesis10.11575/PRISM/27050